Candidate Gene Analysis Reveals Strong Association of CETP Variants With High Density Lipoprotein Cholesterol and PCSK9 Variants With Low Density Lipoprotein Cholesterol in Ghanaian Adults: An AWI-Gen Sub-Study
| Autor: | Godfred Agongo, Lucas Amenga-Etego, Engelbert A. Nonterah, Cornelius Debpuur, Ananyo Choudhury, Amy R. Bentley, Abraham R. Oduro, Charles N. Rotimi, Nigel J. Crowther, Michèle Ramsay, AWI-Gen and H3Africa, H3Africa |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Linkage disequilibrium Candidate gene lcsh:QH426-470 Ghanaians Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine High-density lipoprotein lipid Genetics single nucleotide variant AWI-Gen Genetics (clinical) Original Research Genetic association Cholesterol PCSK9 candidate gene PON1 lcsh:Genetics 030104 developmental biology chemistry 030220 oncology & carcinogenesis Molecular Medicine lipids (amino acids peptides and proteins) Candidate Gene Analysis |
| Zdroj: | Frontiers in Genetics, Vol 11 (2020) Frontiers in Genetics |
| ISSN: | 1664-8021 |
| DOI: | 10.3389/fgene.2020.456661 |
| Popis: | Variations in lipid levels are attributed partly to genetic factors. Genome-wide association studies (GWASs) mainly performed in European, African American and Asian cohorts have identified variants associated with LDL-C, HDL-C, total cholesterol (TC) and triglycerides (TG), but few studies have been performed in sub-Saharan Africans. This study evaluated the effect of single nucleotide variants (SNVs) in eight candidate loci (ABCA1, LCAT, LPL, PON1, CETP, PCSK9, MVK, and MMAB) on lipid levels among 1855 Ghanaian adults. All lipid levels were measured directly using an automated analyser. DNA was extracted and genotyped using the H3Africa SNV array. Linear regression models were used to test the association between SNVs and log-transformed lipid levels, adjusting for sex, age and waist circumference. In addition Bonferroni correction was performed to account for multiple testing. Several variants of CETP, LCAT, PCSK9, and PON1 (MAF > 0.05) were associated with HDL-C, LDL-C and TC levels at p < 0.05. The lead variants for association with HDL-C were rs17231520 in CETP (β = 0.139, p < 0.0001) and rs1109166 in LCAT (β = −0.044, p = 0.028). Lower LDL-C levels were associated with an intronic variant in PCSK9 (rs11806638 [β = −0.055, p = 0.027]) and increased TC was associated with a variant in PON1 (rs854558 [β = 0.040, p = 0.020]). In silico functional analyses indicated that these variants likely influence gene function through their effect on gene transcription. We replicated a strong association between CETP variants and HDL-C and between PCSK9 variant and LDL-C in West Africans, with two potentially functional variants and identified three novel variants in linkage disequilibrium in PON1 which were associated with increasing TC levels in Ghanaians. |
| Databáze: | OpenAIRE |
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